Role of neutrophils in IL-17-dependent immunity to mucosal candidiasis.
Role of neutrophils in IL-17-dependent immunity to mucosal candidiasis.
复制标题
中性粒细胞在IL-17依赖性粘膜念珠菌病中的作用。
DOI：
10.4049/jimmunol.1302265
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发表时间：
2014-02-15
期刊：
影响因子：
--
通讯作者：
Gaffen SL
中科院分区：
文献类型：
--
作者：
Huppler AR;Conti HR;Hernández-Santos N;Darville T;Biswas PS;Gaffen SL
Oropharyngeal candidiasis (OPC), caused by the commensal fungus Candida albicans, is an opportunistic infection associated with infancy, AIDS and IL-17-related primary immunodeficiencies. The Th17-associated cytokines IL-23 and IL-17 are crucial for immunity to OPC, but the mechanisms by which they mediate immunity are poorly defined. IL-17RA-deficient humans and mice are strongly susceptible to OPC, with reduced levels of CXC chemokines and concomitantly impaired neutrophil recruitment to the oral mucosa. Paradoxically, humans with isolated neutropenia are typically not susceptible to candidiasis. To determine whether immunity to OPC is mediated via neutrophil recruitment, mice lacking CXCR2 were subjected to OPC, and were found to be highly susceptible, although there was no dissemination of fungi to peripheral organs. To assess whether the entire neutrophil response is IL-17-dependent, IL-17RA−/− and IL-23−/− mice were administered neutrophil-depleting antibodies and subjected to OPC. These mice displayed increased oral fungal burdens compared to IL-17RA−/− or IL-23−/− mice alone, indicating that additional IL-17-independent signals contribute to the neutrophil response. WT mice treated with anti-Gr-1 antibodies exhibited a robust infiltrate of CD11b+Ly-6GlowF4/80− cells to the oral mucosa, but were nonetheless highly susceptible to OPC, indicating that this monocytic influx is insufficient for host defense. Surprisingly, Ly-6G antibody treatment did not induce the same strong susceptibility to OPC in WT mice. Thus, CXCR2+ and Gr-1+ neutrophils play a vital role in host defense against OPC. Moreover, defects in the IL-23/17 axis cause a potent but incomplete deficiency in the neutrophil response to oral candidiasis.
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影响因子：
4.4
作者：
Gaffen, Sarah L.;Hernandez-Santos, Nydiaris;Peterson, Alanna C.
通讯作者：
Peterson, Alanna C.
影响因子：
15.9
作者：
Eash, Kyle J.;Greenbaum, Adam M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
3.1
作者：
Frazer, Lauren C.;O'Connell, Catherine M.;Darville, Toni
通讯作者：
Darville, Toni
影响因子：
15.9
作者：
Mei, Junjie;Liu, Yuhong;Worthen, G. Scott
通讯作者：
Worthen, G. Scott
影响因子：
2.1
作者：
Farah, C. S.;Lynch, N.;McCullough, M. J.
通讯作者：
McCullough, M. J.